NZB, NZB/W, MRL/1 and BXSB mice develop a spontaneous autoimmune response with age. The development of autoantibodies and the subsequent appearance of immune complex nephritis is similar to abnormalities seen in systemic lupus erythematosus (SLE), and thus these mice provide a useful model for the study of autoimmunity and SLE. A frequent and serious manifestation of SLE is the involvement of the central nervous system (CNS). One hypothesis concerning central nervous system involvement in SLE postulates that brain reactive autoantibodies found in the sera of SLE patients mediate CNS disturbances. Similar brain reactive autoantibodies are found in murine models of SLE, however it is not known whether these mice display CNS abnormalities. It is the objective of the proposed investigations to assess the validity of the hypothesis that brain reactive autoantibodies may mediate CNS involment in autoimmune disease, such as SLE. In general, the hypothesis suggests that immune complex deposits in the choroid plexus may damage the blood-cerebrospinal fluid barrier allowing brain reactive antibodies in the vascular system to gain access to the CNS and interfere with normal brain functioning. The proposed studies will attempt to more fully characterize brain reactive autoantibodies found in the sera of autoimmune mice with respect to their binding specificity toward various brain regions, as well as examine the brain antigens toward which they react. The ability of these anti-brain antibodies to cross the blood-brain barrier in autoimmune mice of various ages, as well as the question concerning whether these antibodies can be found to occur naturally in the brains of these mice will be studied. It is anticipated that such investigations will lead to useful information concerning brain cell surface antigens, the potential effects of immune system components on CNS functioning and, most importantly, the role of anti-brain autoantibodies in mediating autoimmune CNS disease such as occurs in SLE.